3.1. Antioxidant Activity
Antioxidants are stable molecules that scavenge free radicals and maintain a lowered redox state inside cells to prevent or postpone cell damage
[25]. The imbalance between free radicals and antioxidants leads to oxidative-stress-related diseases, such as diabetes, cancers, atherosclerosis, and inflammatory and neurodegenerative diseases
[26]. Recently, several synthetic antioxidants, such as butylated hydroxytoluene and butylated hydroxyanisole, were discovered to be harmful to human health
[26]. As such, the quest for effective, non-toxic, natural substances with potent antioxidative effects has recently intensified.
Studies have shown that there is a substantial relationship between chemical composition and antioxidant activity. In particular, the contents of polyphenols, flavonoids and saponins are responsible for the antioxidant properties. Polyphenolic compounds act as antiradical activity, reducing agents, and complexes of pro-oxidant metals and quenchers of singlet oxygen, promoting the natural antioxidative defense mechanisms and protecting enzyme activity
[27]. The genus
Iris has been proven to contain substantial amounts of phenolic compounds, particularly flavonoids and their derivatives. Therefore, various extracts of this plant have been evaluated for their antioxidant potency.
Mahdinezhad et al.
[28] investigated the in vivo protective effects of
I. germanica L. hydroalcoholic extract at doses of 100 and 200 mg/kg on the liver and pancreas of a streptozotocin-induced diabetic rat model for 4 weeks. Accordingly, the repeated oral administration of the extract lowered the high level of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) compared with diabetic control rats. The extract also improved the liver antioxidant capacity (increase in thiol groups). The protective effect was ascribed to the significant amounts of flavonoids and anthocyanins in the hydroalcoholic extract. The authors supported the use of the plant as a natural antioxidant source to preserve the human body from free-radical-related disorders, especially diabetes mellitus and hepatic injury
[28].
The in vitro antioxidant activity of
Iris has been shown to be significantly correlated with the total content of phenolic compounds. The antioxidant activity of petroleum ether, chloroform and methanol crude extracts of fresh
I. suaveolens Boiss & Reut rhizomes was tested using the β-carotene–linoleic acid and CUPRAC techniques; quercetin and butylated hydroxytoluene (BHT) served as positive controls
[29]. The results disclosed that both petroleum ether and chloroform extracts exhibited pronounced antioxidant potency. Thirteen phenolic and flavonoid compounds were isolated from the petroleum ether and chloroform extracts and were screened in vitro for their antioxidant effects. Coniferaldehyde, a phenolic compound obtained from the chloroform extract, displayed the greatest activity among all the investigated compounds at 25 and 50 mg/mL in both β-carotene-bleaching and CUPRAC systems
[29].
Moreover, the aqueous and ethanol extracts of
I. germanica L. were evaluated for their in vitro antioxidant activity using several testing systems, namely, free radical scavenging, reducing power, superoxide anion radical scavenging, metal chelating activities and hydrogen peroxide scavenging
[30]. The results indicated that at concentrations of 15, 30 and 50 µg/mL both aqueous and ethanol fractions exhibited excellent antioxidant properties, displaying 95.9, 88.4 and 79.9% and 90.5, 78.0 and 65.3% inhibition of peroxidation of linoleic acid emulsion, respectively. At concentrations of 20, 40 and 60 µg/mL, both extracts showed remarkable reducing power, free radical scavenging, hydrogen peroxide scavenging, metal chelating and superoxide anion radical scavenging activities
[30].
Similarly, the antioxidant activity of the ethanolic extracts
I. germanica L. areal parts and rhizomes was assessed using free radical DPPH scavenging and β-carotene–linoleic acid assays
[31]. The results showed that, in the DPPH system, the aerial part and rhizome extracts exhibited significant IC
50 values of 5.38 and 12.3 mg/mL, respectively, while at the concentration of 3.15 mg/mL, the total antioxidant activity of the extracts was 98.7% and 97.4%, respectively
[31].
In a recent study, the antioxidant activity of the petroleum ether, ethyl acetate and methanol extracts of
I. ensata leaves was analyzed using various antioxidant assays such as the DPPH radical scavenging assay and FRAP (ferric ion reducing assay)
[32]. Accordingly, all the extracts exhibited pronounced antioxidant potential. In addition, the research reported that the IC
50 values decreased with the increase in polarity. In the ferric reducing assay, the IC
50 values of the three extracts were found to be 226.66, 188.94 and 124.63 µg/mL, respectively
[32].
The genus Iris contains substantial amounts of glycosylated flavonoids and phenolic acids, which are, generally, water-soluble products and can be detected in great quantities in the bloodstream, thus exhibiting high oral bioavailability. Due to all these properties, polyphenols are involved in a wide range of biological effects, such as antibacterial, anti-inflammatory, antiallergic, hepatoprotective, antiviral, antithrombotic, anticarcinogenic, cardioprotective and vasodilatory effects.
3.2. Anticancer Activity
Recently, the use of anticancer drugs has been hampered by the emergence of several impediments, with these mostly being the cellular resistance to chemotherapy drugs and toxicities
[33]. Therefore, the global trend is being shifted toward medicinal plants and plant-based compounds owing to their accessibility, affordability and effectiveness
[33]. Several
Iris-based compounds have been isolated from various extracts and tested in vitro (
Table 2) for their cytotoxicity and chemopreventive activities (
Figure 2).
Figure 2. General approach applying to assess the anticancer effect of
Iris spp. in vitro.
Irilone, iriflogenin, genistein and iris kashmirianin are only a few of the flavonoids isolated from
I. germanica L. that have been shown to exert chemopreventive benefits by reducing cytochrome P450 1A activity and enhancing NAD(P)H: quinone reductase (QR)activity
[16].
Alam et al.
[34] evaluated the cytotoxicity potential of glycosides and isoflavonoids newly isolated from the rhizomes of
I. kashmiriana Baker against several cancer cell lines, namely, MCF-7 and MDA-MB-231 (breast cancer), HeLa (cervical cancer), PC-3 (prostate cancer) and A-549 (lung cancer), using the MTT cellular viability assay. Accordingly, the compounds 5,7,8-trihydroxy-3-(4-methoxyphenyl)-
4H-chromen-4-one,5,7,8-trihydroxy-3-(4-hydroxyphenyl)-
4H-chromen-4-one,5,7,8-triacetoxyoxy-3-(4-methoxyphenyl)-
4H-chromen-4-one and 6,7-diacetoxyoxy-3-(4-methoxyphenyl)-
4H-chromen-4-one showed prominent anticancer activity against all cell lines, with IC
50 values ranging from 3.8 to 5.6 mg/mL. These compounds were also found to induce cell-cycle block at the G2/M phase
[34].
Similarly, Tantry et al.
[35] studied the in vitro cytotoxicity activity of a new alkylated 1,4-benzoquinone derivative obtained from the chloroform extract of
I. nepalensis rhizomes against various cancer cell lines using the MTT colorimetric assay. The compound revealed remarkable cytotoxicity against HCT116 (colon carcinoma), HL-60 (blood cancer) and ZR-75 (breast cancer), with IC
50 values of 10 ± 1.1002, 34 ± 1.1205 and 31 ± 1.1001, respectively. Likewise, the cytotoxicity potential of two flavonoids, 7-
O-methylaromadendrin and tectorigenin, as well as four iridal-type triterpenes, iritectols A and B, isoiridogermanal and iridobelamal A, isolated from the rhizomes of
I. tectorum Maxim were assessed against four cancer cell lines using the SRB method (sulphorhodamine B)
[36]. The results indicated that iritectol B, isoiridogermanal and iridobelamal A displayed identical cytotoxicity against both MCF-7 and C32 cell lines, with IC
50 values for a range of 11 µM and 23 µM. Moreover, they found that iritectol B exhibited a dose-dependent apoptotic effect against COR-L23, while both 7-
O-methylaromadendrin and tectorigenin flavonoids were discovered to be capable of triggering cell-cycle arrest at the S and G2/M phases, respectively (
Table 2). In vivo experiments based on animal models and molecular targets involved in the anticancer effects studies are mandatory to confirm the anticancer potential of
Iris spp.
Table 2. In vitro anticancer and cytotoxic activities of Iris spp. extracts against various cell lines.
| Species |
Parts |
Extract |
Cancer Type |
Cell Line |
Method |
IC50 |
Results |
References |
| I.nertschinskia Lodd. |
Rhizomes |
EtOH |
Breast |
MCF-7 |
TBE |
- |
Induced apoptosis; triggered cell cycle block at G1 phase; ↑ p53 phosphorylation in a dose-dependent fashion; ↑ Bax expression; induced caspase-7 cleavage. |
[17] |
| I.nertschinskia Lodd. |
Whole plant |
EtOH |
Breast |
Hs578T |
TBE |
- |
Triggered apoptosis hallmarked by cells accumulation in the sub-G 1 phase. |
[37] |
| MDA-MB-231 |
| I. pseudopumila Tineo |
Rhizomes |
PET |
Breast |
MCF-7 |
SRB |
48 h |
96.79 µg/mL |
Induced potent cytotoxic effects against the three cell lines. |
[38] |
| Skin |
C32 |
57 ± 1.04 µg/mL |
| Kidney |
ACHN |
99 ± 1.95 µg/mL |
| I. variegata L. |
Rhizomes |
H2O |
Skin |
IGR39 |
MTT |
0.53 mg/mL |
Reduced significantly cell viability; the ethanolic extract was shown to be more efficient against both cell lines. |
[39] |
| Breast |
MDA-MB-231 |
0.33 mg/mL |
| I. hungarica Waldst. & Kit. |
H2O |
Skin |
IGR39 |
1.15 mg/mL |
| Breast |
MDA-MB-231 |
0.57 mg/mL |
| 70% EtOH |
Skin |
IGR39 |
0.53 mg/mL |
| Breast |
MDA-MB-231 |
0.33 mg/mL |
| I. pseudopumila Tineo |
Rhizomes |
MeOH |
lung |
CORL-23 |
MTT |
31.5 ± 2.6 µg/mL |
Both extracts revealed strong antiproliferative effects towards both cell lines. |
[40] |
| Skin |
C32 |
48.7 ± 2.6 µg/mL |
| Flowers |
lung |
CORL-23 |
25.4 ± 2.6 µg/mL |
| Skin |
C32 |
50.9 ± 2.6 µg/mL |
| I. Spuria L. |
Rhizomes |
MeOH |
Lung |
A549 |
MTT |
123.04 µg/mL |
All extracts displayed a dose dependent inhibitory potential against both cell lines A549, and Caco-2. |
[41] |
| Colon |
Caco-2 |
302.94 µg/mL |
| I. kashmiriana Baker |
Lung |
A549 |
128.7µg/mL |
| Colon |
Caco-2 |
237.76 µg/mL |
| I. germanica L. |
Lung |
A549 |
134.72 µg/mL |
| Colon |
Caco-2 |
230.82 µg/mL |
| I. crocea Jacquem. ex R.C.Foster |
Lung |
A549 |
149.80 µg/mL |
| Colon |
Caco-2 |
368.88µg/mL |
| I. ensata Thunb. |
Lung |
A549 |
137.98 µg/mL |
| Colon |
Caco-2 |
358.81 µg/mL |
| I. kashmiriana Baker |
Whole plant |
MeOH |
Lung |
A549 |
MTT |
128.7 µg/mL |
The ethanol extract exhibited a dose-dependent selective antiproliferative effect on epithelial cancers. |
[42] |
| Colon |
Caco-2 |
237.76 µg/mL |
| I. hungarica |
Rhizomes |
H2O |
Colon |
HCT116 |
MTT |
42.3 µg/mL |
Cell lines HCT116, HeLa, HL-60 were sensitive to the plant aqueous extract. The highest cytotoxicity was noticed against HL-60. |
[43] |
| Cervical |
HeLa |
78.7 µg/mL |
| Leukemia |
HL-60 |
3.6 µg/mL |